tbuckley/cabot-search huggingface dataset:
NIMG-42. DURABLE OVERALL RESPONSE RATE (ORR) TARGETS FOR RECURRENT GLIOBLASTOMA (RGBM) CLINICAL TRIALS BASED ON THE HISTORIC ASSOCIATION BETWEEN ORR AND MEDIAN OVERALL SURVIVAL (MOS)
Authors: Benjamin Ellingson, Patrick Y Wen, Susan Chang, Martin van den Bent, Michael Vogelbaum, Gang Li, Shanpeng Li, Jiyoon Kim, Gilbert Youssef, Wolfgang Wick, Andrew Lassman, Mark Gilbert, John de Groot, Michael Weller, Evanthia Galanis, Timothy Cloughesy
Journal: Neuro-Oncology (2022)

Abstract Durable overall response rate (ORR) remains a meaningful endpoint in recurrent GBM; however, the target ORR for single arm recurrent GBM trials has not been based on historic information or tied to patient outcomes. The current study reviewed past trials in recurrent GBM in order to judiciously define target ORRs for use in recurrent GBM trials. After reviewing 69 treatment arms comprising 4,971 patients, ORR was 6.1%[95% CI 4.23; 8.76%] for cytotoxic chemotherapies (ORR=7.59% for CCNU, 7.57% for TMZ, 0.64% for CPT-11, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for immunotherapies (select trials), and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2=0.4078, P&amp;lt; 0.0001), biologics (R2=0.4003, P=0.0003), and immunotherapy trials (R2=0.8994, P&amp;lt; 0.0001), but not anti-angiogenic agents (R2=0, P=0.8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2=0.3164, P&amp;lt; 0.0001; mOS[weeks]=0.6xORR+28.9), suggesting an ORR &amp;gt;20% results in an mOS of &amp;gt; 40.9 weeks, which is double the survival estimate of a treatment with ORR=0% and ≥ 2 months longer than treatments with ORR=5%. Assuming an ineffective therapy (control) has ORR=5%, a trial of 32 patients with a target ORR=20% leads to the 95% confidence interval higher than the control group. We conclude that single arm phase II studies in recurrent GBM with ≥ 32 patients should have a target ORR ≥ 20%. This was associated with a median OS of approximately 1 year. Importantly, durability of response should also be considered and was not assessed in the current meta-analysis.
CTIM-17. EO2401 THERAPEUTIC VACCINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA: PHASE 1/2 ROSALIE STUDY (NCT04116658)
Authors: David A Reardon, Ahmed Idbaih, Maria Vieito, Ghazaleh Tabatabai, Agostina Stradella, François Ghiringhelli, Michael C Burger, Iris Mildenberger, Macarena González, Alice Hervieu, Marta Gil Martin, Mirjam Renovanz, Mehdi Touat, Patrick Y Wen, Antje Wick, Cécile Gouttefangeas, Ana Maia, Christophe Bonny, Jan Fagerberg, Wolfgang Wick
Journal: Neuro-Oncology (2022)

Abstract EO2401 includes microbial-derived, synthetically produced HLA-A2 restricted peptides with molecular mimicry to antigens (IL13Rα2, BIRC5 and FOXM1) upregulated in glioblastoma, and the CD4 helper peptide UCP2. Patients with glioblastoma at first progression received EO2401 (300µg/peptide, q2weeks x4 then q4weeks), EO2401+nivolumab (3mg/kg q2weeks), or E02401+nivolumab+bevacizumab (10mg/kg q2weeks). Cohort-1 included EO2401x2 then EO2401+nivolumab. EO2401+nivolumab was evaluated in Cohort-2a, as adjuvant treatment in Cohort-2b, and as neoadjuvant/adjuvant treatment in Cohort-2c. Cohort-3 assessed EO2401+nivolumab+bevacizumab. Part 1 included 40 patients (Cohort-1/3, Cohort-2a/23, Cohort-2b/3, Cohort-3/11). Part 2 allowed low-dose-bevacizumab (5mg/kg q2weeks) for symptomatic edema and enrolled 38 patients (Cohort-1/18, Cohort-2a/15, Cohort-2b/3; and recruiting Cohort-2c/2 target 6, Cohort-3/0 target 15).Safety assessment of part 1 showed EO2401+nivolumab+/-bevacizumab to be well tolerated with EO2401 associated toxicity limited to local administration site reactions (48%; all grade 1-2). The nivolumab-/bevacizumab-toxicity was consistent with historical single-agent data. Strong CD8 T cell ELISPOT responses against the 3 vaccine peptides and cross-reactivity against targeted antigens was demonstrated in the majority of evaluable patients. Immune response was confirmed with tetramer staining of specific CD8 either ex vivo or after in vitro stimulation. For part 1, median progression-free survival (mPFS), and median survival (mOS) for EO2401+nivolumab (Cohorts-1/2/2b, n=29 median follow-up [mFU] 14.0 months) were 1.8 and 10.6 months. Patients on EO2401+nivolumab+bevacizumab (n = 11 mFU 9.6 m) had mPFS 5.5 months and 9 patients alive 7-12.4 months. Objective Response Rate/Disease Control Rate for EO2401+nivolumab and EO2401+nivolumab+bevacizumab was 10%/34% and 55%/82%.Median treatment duration for Cohort-2a part 1 was 6.1 weeks (1/23 on treatment), while it was 10.0 weeks (8/15 on treatment) for Cohort-2a part 2. Overall, in part 2, 36% received low-dose-bevacizumab.EO2401 generated strong immune responses and was well tolerated. Addition of standard bevacizumab to EO2401+nivolumab improved PFS and tumor response. Symptom driven low-dose-bevacizumab supported longer treatment durations. Outcome of study part 2 will be presented.
EXTH-91. GALECTIN-3 INHIBITOR PAIRED WITH FOCAL LOW-INTENSITY NONINVASIVE TDCS CAN ACHIEVE MAXIMAL THERAPEUTIC BENEFIT IN CLINICALLY RELEVANT MENINGIOMA MOUSE MODELS
Authors: Arabinda Das, Daniel G McDonald, Milad Yazdani, Connor Stephenson, Shikhar Mehrotra, Cynthia A Welsh, Libby Kosnik Infinger, William A Vandergrift, Abhay K Varma, Sunil J Patel, Pierre Giglio, Alicia Zukas, David Cachia, Scott M Lindhorst
Journal: Neuro-Oncology (2022)

Abstract Atypical and anaplastic meningiomas (WHO Grade 2 and WHO Grade 3 respectively) represent a subgroup of meningiomas that tend to have higher rates of recurrence with associated’s higher morbidity and mortality than the more common WHO Grade 1 meningiomas. Our laboratory data demonstrated that galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in these meningioma subtypes as compared to normal brain tissue. However, the root of the profoundly immunosuppressive tumor microenvironment in meningioma cells is not fully understood. To address this, we used a Gal-3 inhibitor TD 139 paired with low-intensity non-invasive transcranial direct current stimulation (tDCS) to suppress tumor growth and enhance the immune response in the preclinical model. Treatment of tDCS (50 mV/mm for 30 min) followed by 1 mM of TD139 induced cell death in anaplastic meningioma in vitro human triple co-culture model but has no effect on mouse cortical neurons. Furthermore, we demonstrated that inhibiting of Gal-3 expression significantly decreased the protein levels of urokinase-type plasminogen activator receptor as well as phosphorylation of Akt and upregulates Bax expression. Treatment with TD139 (1mg/kg per day for 14 days) with tDCS [350 μA (1 x 30 min/day) for 7 times (within 14 Days) showed a significantly (∼60%) decrease in MGS2 atypical meningioma tumor growth in orthotopic allograft model (at Day 41). The percent survival of tumor-bearing mice treated with TD139 and tDCS was significantly higher than an untreated tumor or single treatment. Following TD139 plus tDCS treatment, our results demonstrated significant meningioma cell death via a decrease in NDRG4 (Meningioma marker) and were associated with downregulation of Ki-67 in treated tumors. Based on our substantial preliminary data, we believe that this proposed translational work has the potential to be an effective combinational modality form of treatment for atypical and malignant meningiomas.
NIMG-101. COMPARISON OF PRE-SURGICAL MRI FINDINGS FROM LONG-TERM (≥ 3 YRS) VERSUS SHORT-TERM (&amp;lt; 3 YRS) GLIOBLASTOMA SURVIVORS: A BLINDED, CASE-CONTROL REVIEW
Authors: Edina Komlodi-Pasztor, Nicole Briceno, Elizabeth Vera, Anna Choi, Alexa Christ, Ewa Grajkowska, Heather Leeper, Matthew Lindsley, Kathleen Wall, Karen Evans, Tricia Kunst, Kelly Mentges, Jennifer Reyes, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Jing Wu, Lily Polskin, Terri Armstrong, Mark Gilbert, James Smirniotopoulos
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND The median overall survival of patients with glioblastoma (GBM) is 10-12 months and the five-year survival ranges from 5-10%. Favorable clinical and molecular prognostic markers have been described in the literature, although an individual patient’s prognosis cannot easily be predetermined on these features as shown in the NOB-LTS project by Briceno et al. (SNO 2021). Until now, no radiologic characteristics have been correlated with better patient outcomes. We reviewed eighteen MRI features to determine if these could aid the identification of long-term survivors (LTS). METHODS From the NOB-LTS cohort of our Natural History Study, 16 long-term survivals (LTS; ≥ 3 years survival post-diagnosis) were matched based on sex, age, and extent of resection to 32 control (STS, &amp;lt; 3 years survival post-diagnosis) patients with NGS-confirmed IDH-wt glioblastoma. Pre-surgical MRIs (T1, T1 post-contrast, T2, T2/FLAIR, DWI, ADC) were reviewed by three blinded reviewers and analyzed based on pre-set criteria. RESULTS T1 hypointensity occurred commonly in the LTS (71%) vs STS (29%) while central heterogeneous signal occurred commonly in the STS (73%) vs LTS (50%) patients. Restricted diffusion was seen in 82% of STS and 70% of LTS cases. No difference was seen in irregular enhancement, peripheral and grey matter enhancement on T1 post-contrast images. Evaluation of T2/FLAIR images showed no difference in the number of lobes involved, presence of mass effect, heterogeneity of the signal or the perilesional signal abnormality or involvement of grey matter. CONCLUSION Our results suggest that pre-surgical MRI might be a useful prognostic tool as T1 hypointensity more frequently, and T1 central heterogeneity less commonly seen in the LTS group. These imaging findings may provide additional insights regarding the differences in tumor biology between LTS and STS. Further validation and correlation with histological/molecular characteristics are planned to better predict patient outcomes with newly diagnosed glioblastoma.
CTIM-26. PHASE II TRIAL OF SURVAXM PLUS TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Manmeet Ahluwalia, Michael J Ciesielski, David A Reardon, Ajay Abad, William Curry, Eric Wong, David Peereboom, Sheila Figel, Alan Hutson, Adrienne Groman, Henry Withers, Song Liu, Ahmed Belal, Jingxin Qiu, Kathleen Mogensen, Cathy Schilero, Atulya Khosla, Danielle Casucci, Laszlo Mechtler, Robert Fenstermaker
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Newly diagnosed glioblastoma (nGBM) has dismal outcomes with survival of 15-18 months. Tumor associated “survivin” is expressed in &amp;gt; 95% of nGBM and targetable by SurVaxM immunotherapy. METHODS nGBM patients (pts) were enrolled in this Phase 2 study, age ≥ 18, KPS ≥ 70, IHC confirmed surviving-expression, expression of HLA-A*02, A*03, A*11 or A*24 MHC-I alleles and residual contrast enhancement of ≤1 cm3 by MRI. Pts were treated with standard TMZ chemoradiation followed by initiation of 4 priming doses of SurVaxM (500 mcg in emulsion with Montanide ISA 51, every 2 weeks) with 100 mcg sargramostim. Maintenance doses of SurVaxM-Montanide plus sargramostim given every 12 weeks with Adjuvant TMZ for at least 6 cycles. The primary endpoint was 70% progression free survival (PFS) at 6 mos. Primary analyses of median PFS (mPFS) and median overall survival (OS) were measured from the first immunization. Safety, tolerability, and immune responsiveness were also determined. RESULTS 63 pts (38 males), median age, 60 years were treated at 5 sites. SurVaxM was well tolerated, with no serious adverse events. A strong positive correlation, accounting for censoring, was observed between PFS and OS of all pts (r = 0.79; 95% CI (0.66,0.87)). SurVaxM was immunogenic and produced survivin-specific CD8+ T-cells and antibody (IgG) titers in both methylated and unmethylated MGMT pts. Both groups showed clinical benefit with PFS of 11.4 months for the for the whole group, 7.0 months for unmethylated and 17.9 months for methylated group. OS of 25.9 months for the whole group, 16.5 months for unmethylated and 41.4 months for methylated group. CONCLUSIONS SurVaxM appeared to be safe and well-tolerated in pts with nGBM. SurVaxM was effective at stimulating survivin-specific immune responses and the primary endpoint was met. SurVaxM represents a promising therapy for nGBM, randomized trial is ongoing. Clinical trial information: NCT02455557.
RADT-15. 18F-DOPA PET/CT SURVEILLANCE FOR GLIOBLASTOMA: A RADIOMIC MODEL FROM A PROSPECTIVE PHASE II CLINICAL TRIAL PREDICTING SURVIVAL IN IDH-WILDTYPE, MGMT-UNMETHYLATED PATIENTS
Authors: Jing Qian, Deanna Pafundi, William Breen, Paul Brown, Christopher Hunt, Mark Jacobson, Derek Johnson, Timothy Kaufmann, Bradley Kemp, Sani Kizilbash, Val Lowe, Michael Ruff, Jann Sarkaria, Joon Uhm, Hok Seum Wan Chan Tseung, Elizabeth Yan, Yan Zhang, Nadia Laack, Debra Brinkmann
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Interpretation of serial magnetic resonance imaging (MRI) for glioblastoma following radiation therapy (RT) is complicated by difficulty differentiating tumor from treatment-related changes, even using updated RANO criteria. The incorporation of novel imaging such as 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET/CT to post-treatment serial imaging may improve prognostication and better facilitate future treatment decisions. METHODS The secondary analysis of a recent phase II prospective clinical trial of 18F-DOPA PET/CT-directed dose-escalated RT included patients with IDH-wildtype, MGMT-unmethylated glioblastoma who underwent post-treatment serial 18F-DOPA PET/CT surveillance. Quantitative features were extracted from pre-RT and post-RT serial PET/CT images, and robust prognostic features were selected using an in-house workflow. Both an automated machine learning (ML) algorithm and an interpretable ML algorithm were utilized to correlate surveillance PET image features with subsequent survival of greater than 12 months versus less than 12 months from the surveillance timepoint. Changes from pre-RT to post-RT PET/CT (delta model) were also assessed for association with post-RT survival and validated with a separate cohort. RESULTS Thirty-five patients with IDH-wildtype, MGMT-unmethylated glioblastoma who had at least one available (range: 1-14) post-treatment 18F-DOPA PET/CT were included. Twenty-four were used for model training, while 11 were used for validation. Ultimately, a five-feature post-RT model utilizing two shape, two texture, and one first-order radiomic feature was selected. For the delta model, five texture, two shape, and one first order radiomic feature were selected. The models show 90% accuracy in predicting survival &amp;lt; 12 months post-surveillance on the training set, and 68%-73% accuracy (AUC 0.64-0.73) for the validation cohort. Delta features were significantly associated with overall survival (p &amp;lt; 0.05). CONCLUSIONS Post-RT serial 18F-DOPA PET/CT imaging can help distinguish true tumor progression in patients with glioblastoma using a radiomics model. Tumor response evaluated for changes from pre-RT to post-RT 18F-DOPA PET/CT also predicted subsequent overall survival.
RADT-33. INTRATUMORAL HEMORRHAGE IN VESTIBULAR SCHWANNOMAS FOLLOWING GAMMA KNIFE STEREOTACTIC RADIOSURGERY
Authors: Othman Bin-Alamer, David Fogg, Zhishuo Wei, James Duehr, Arka Mallela, Ajay Niranjan, L Dade Lunsford, Hussam Abou-Al-Shaar
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Intratumoral hemorrhage (ITH) is a rare occurrence in vestibular schwannomas (VS) resulting in worsening vestibular and cranial nerve deficits. Scarce data described the occurrence, management, and outcomes of ITH after stereotactic radiosurgery (SRS). OBJECTIVE The aim of this study is to delineate the incidence, presentation, management, and outcomes of ITH in VS patients following SRS. METHODS A total of 2058 patients with VS underwent Gamma Knife radiosurgery (GKRS) at the University of Pittsburgh Medical Center between 1987 and 2022. The authors identified patients with ITH. Their presentation, management, clinical, and imaging outcomes are reported and analyzed. RESULTS A total of 1902 VS patients had sufficient clinical and imaging follow-up data. Five Koos III (n = 1) and IV (n = 4) VS patients developed ITH after GKRS, resulting in a cumulative incidence rate of 0.26%. The age at presentation ranged from 62 to 79 years, and 3 of the patients were males. The time from VS diagnosis to GKRS ranged from 1-13 months, and the time from GKRS to ITH ranged from 2-130 months. Three patients had bleeding risk factors. One patient required urgent surgical intervention due to the ITH volume, while the other four patients initially were observed. Three remained stable and required no delayed intervention. Histopathological analysis revealed multiple fragments of S-100–positive cells, hemorrhage, and hemosiderin-laden macrophages. At last follow-up, 4 patients had clinically improved, and one remained stable.ConclusionVS ITH following SRS is a rare complication with a cumulative incidence rate of 0.26%. Patient-tailored management is vital based on patient presentation, acuity, and ITH size and characteristics.
SURG-23. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR NEWLY DIAGNOSED AND RECURRENT IDH WILD-TYPE GLIOBLASTOMA
Authors: John de Groot, Albert Kim, Sujit Prabhu, Ganesh Rao, Adrian Laxton, Peter Fecci, Barbara O'Brien, Andrew Sloan, Veronica Chiang, Stephen Tatter, Alireza Mohammadi, Dimitris Placantonakis, Roy Strowd, Clark Chen, Constantinos Hadjipanayis, Mustafa Khasraw, David Sun, David Piccioni, Kaylyn Sinicrope, Jian Campian, Sylvia Kurz, Brian Williams, Kris Smith, Zulma Tovar-Spinoza, Eric Leuthardt
Journal: Neuro-Oncology (2022)

Abstract Treatment options for glioblastoma remain limited, particularly for those who are not eligible for traditional resection, whether due to lesion location or inability to tolerate open craniotomy. Maximal-safe resection followed by radiation with concurrent and adjuvant temozolomide offers the best outcomes for patients. Unfortunately, not all tumors are amenable to conventional surgical resection at the time of diagnosis with only about 1/3 of patients able to receive a gross-total resection and 15-25% of patients receiving biopsy only, thus reducing their projected overall survival to 9 months. Laser interstitial thermal therapy (LITT) is a minimally invasive, cytoreductive tool, that has demonstrated safety as a surgical approach to treat primary brain tumors. METHODS Data from LAANTERN prospective multicenter registry (NCT02392078) was analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma (N=89). Demographics, intraprocedural data, adverse events, KPS, health-economics, and survival data were prospectively collected then analyzed separately for newly diagnosed GBM (N=29) and recurrent GBM (N=60). RESULTS Median overall-survival was 9.73 months (95% CI: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 (6.94, 12.36) months for recurrent patients. Median overall-survival for newly diagnosed patients receiving post-LITT chemoradiotherapy was 16.14 months (6.11, not reached). The median length of hospital stay was 50 hours and 80% of patients were discharged to home. CONCLUSIONS LITT offers an effective cytoreductive approach for patients with newly diagnosed and recurrent IDH wild-type glioblastoma. Importantly, its use in newly diagnosed patients who receive post-LITT chemoradiotherapy leads to a median OS similar to that of patients treated with conventional surgical resection. LITT remains an important alternative for patients with inoperable tumors or those not amenable to resection. Enrollment in LAANTERN is ongoing and these cohorts will be revisited as data continues to mature. Benefits beyond cytoreduction are also being actively explored.
CNSC-02. BREAST TO BRAIN METASTASIS IS EXACERBATED WITH CHEMOTHERAPY THROUGH BLOOD-CEREBRAL SPINAL FLUID-BARRIER AND INDUCES ALZHEIMER’S-LIKE PATHOLOGY
Authors: Josh Neman, Behnaz Saatian, Krutika Deshpande, Vahan Martisorian, Peter LaViolette, Adrienne Boire, Frances Chow, Kyle Hurth, Peter Fecci, Mark Shiroishi, Rachel Eisenbarth
Journal: Neuro-Oncology (2022)

Abstract Control of breast to brain metastasis remains an urgent unmet clinical need. While chemotherapies are essential in reducing systemic tumor burden, they have also shown to promote non-brain metastatic invasiveness and drug-driven neurocognitive deficits through formation of neurofibrillary tangles (NFT) independently. Now, in this study we investigated the effect of chemotherapy on brain metastatic progression and promoting tumor-mediated NFT. Results show chemotherapies promote increased brain-barrier permeability and facilitate enhanced tumor infiltration, particularly through the blood-cerebrospinal fluid-barrier (BCSFB). This is attributed to increased expression of matrix metalloproteinase 9 (MMP9) which, in turn, mediates loss of Claudin-6 within the choroid plexus cells of the BCSFB. Importantly, increased MMP9 activity in the choroid epithelium following chemotherapy results in cleavage of Tau released from breast cancer cells. This cleaved Tau forms tumor-derived NFT that further destabilize the BCSFB. Our results underline for the first time the importance of the BCSFB as a vulnerable point of entry for brain-seeking tumor cells post-chemotherapy and indicate that tumor cells themselves contribute to Alzheimer’s-like tauopathy.
PATH-03. IMPACT OF GAP-43 AND ACTIN EXPRESSION ON THE OUTCOME AND OVERALL SURVIVAL IN DIFFUSE AND ANAPLASTIC GLIOMAS
Authors: Aleksandrs Krigers, Matthias Demetz, Patrizia Moser, Johannes Kerschbaumer, Konstantin Brawanski, Helga Fritsch, Claudius Thomé, Christian Freyschlag
Journal: Neuro-Oncology (2022)

Abstract Background. Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli (TMs), where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial epidemiologic, radiological and neuropathological prognostic factors. Methods. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. Clinical, neuropathological as well as follow-up-data were gained from the institutional neuro-oncological database. Results. 118 patients with a median age of 46 years (IqR: 35 – 57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. 96 (82%) cases presented with intermediate or strong GAP-43 expression and 78 (67%) with no or light actin expression. Tumors with higher expression of GAP-43 (p=0.024, HR=1.71/rank) and actin (p&amp;lt; 0.001, HR=2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of both proteins: GAP-43 (p=0.009) and actin (p&amp;lt; 0.001). The same was confirmed for anaplasia (GAP-43 p=0.028, actin p=0.029), higher proliferation rate (GAP-43 p=0.016, actin p=0.038), contrast-enhancement in MRI (GAP-43 p=0.023, actin p=0.037) and age (GAP-43 p=0.004, actin p&amp;lt;0.001). Conclusions. The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with oncologically unfavorable prognostic features.